The present invention relates to a novel method for producing a sulfated lactosamine oligosaccharide. In particular, the present invention relates to a method for producing a sulfated lactosamine oligosaccharide from a lactosamine oligosaccharide based on the use of an enzyme reaction.
Sugar chains composed of lactosamine backbones serve as the ligand sugar chain which has the ability to bind cell adhesion molecules belonging to the selectin family, and thus they express important physiological activities in vivo. It has been clarified that expression of such sugar chains on cell surfaces participates in specific adhesion between heterogeneous cells. Functional activating agents and suppressing agents based on the utilization of these sugar chains are expected to be useful drugs. Namely, it is believed that these sugar chains include their principal compound of sialyl Lewis.sup.X (SLe.sup.X) and its analogs with which the selectin molecule is blocked to inhibit adhesion between lymphocyte and endothelial cell, and thus they are useful to mitigate various diseases associated with inflammation. In addition, it is also believed that these sugar chains participate in adhesion to endothelial cells upon hematogenous metastasis of tumor cells, and they participate in adhesion to target cells upon infection with microorganisms. Therefore, these sugar chains are regarded to be important as materials to develop pharmaceuticals for preventing such diseases.
On the other hand, one of the ligands for L-selectin (expressed on lymphocyte) which participates in homing of lymphocyte and rolling of leukocyte caused at an initial stage of inflammation is considered to be "GlyCAM-1 (highly glycosylated cell adhesion molecule-1, glycosylation-dependent cell adhesion molecule-1; expressed on blood vessel endothelium)", and the sugar chain occupies not less than 70% of GlyCAM-1. Recently, GlyCAM-1 attracts great attention together with a basic backbone of the sugar chain (NeuAc-Gal(6S)--(Fuc-)GlcNAc--R, wherein NeuAc represents an N-acetylneuraminic acid residue, Gal represents a galactose residue, (6S) indicates that hydroxyl group at C-6 position is sulfated, Fuc represents a fucose residue, GlcNAc represents an N-acetylglucosamine residue,--represents a glycoside linkage, and R represents a hydrogen atom or a sugar chain: this basic backbone is hereinafter referred to as "basic backbone of GlyCAM-1 sugar chain", if necessary).
GlyCAM-1 and the basic backbone of its sugar chain are expected to play important roles in development of novel pharmaceuticals and in studies on physiological activities in vivo. It is desired to stably supply these substances. However, at present, they can be obtained only from animals which express GlyCAM-1. Therefore, obtainable amounts are minute. It is difficult to produce GlyCAM-1 and the basic backbone of its sugar chain by means of organic synthesis. However, no method has been known for producing a sulfated lactosamine oligosaccharide which can be converted into the basic backbone of the GlyCAM-1 sugar chain.
The present invention has been made taking the aforementioned viewpoints into consideration, an object of which is to provide a novel method for producing a sulfated lactosamine oligosaccharide in order to obtain the basic backbone of the GlyCAM-1 sugar chain.